The purpose of this FOA is to support exploratory studies developing or using novel tools or technologies or testing novel hypotheses to investigate mechanistic questions in HIV infection, replication, latency, and/or pathogenesis (including neuroHIV) in the context of Substance Use Disorders (SUDs). This initiative focuses on exploration and characterization of signaling pathways that are involved in CNS HIV establishment and expansion. The FOA aims to promote research to investigate the underlying molecular mechanisms by which HIV infection is initiated, established, and maintained in the CNS and to determine how addictive substances modulate HIV infection, latency and the size and persistence of CNS HIV reservoirs.
Despite the impressive success of antiretroviral therapy (ART) in reducing HIV-1 associated mortality, ART is unable to fully eliminate latent HIV reservoirs in patients, including in the CNS. There is much that remains to be understood regarding the establishment and persistence of the latent CNS reservoir as well as the effects of inflammation, ART, or the blood brain barrier on this reservoir as well as HIV pathogenesis in the CNS. As an added layer of complexity, addictive substances have the potential to impact HIV infection, establishment and maintenance of latency, and/or disease progression including inflammation and neuroHIV. For example, chronic exposure to addictive substances may disrupt blood brain barrier permeability which could impact viral CNS entry. Addictive substances may also influence the establishment or maintenance of HIV latency of the CNS or alter systemic or localized inflammation which could impact HIV disease progression. Individuals with substance use disorders (SUDs) may have decreased adherence to ART medications which may impact CNS viral replication or latency. Interactions between HIV disease, antiretroviral therapy, and addictive substances greatly complicate our ability to understand and treat HIV in individuals with SUDs. Exploratory studies are needed to develop or apply novel tools or technologies or to test novel hypotheses to order to obtain a deeper understanding of the mechanistic interactions between HIV disease, ART, SUDs, and SUD therapies.
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